This invention relates to the optical detection of glucose in body fluids, particularly in blood. It is concerned especially with in vivo detection in which a detection device is applied to part of the body, or a part of the body to the device, and a signal generated indicating the glucose concentration level in a non-invasive manner.
There are two primary known optical techniques by which the concentration of glucose (or any other analyte) can be detected. One involves the direct measurement of the transmitted intensity of light at the various ligand vibrational wavelengths, and relating this to the molecular concentration by the Beer-Lambert law, for example, modified to allow for scattering. The other exploits the fact that solutes such as glucose modify the water vibration and combination of overtone lines in unique ways. This is because of water molecule clustering effects around the solute molecules. Because many water molecules are involved for each solute molecule, the effect is quite large and likely to offer better sensitivity than the direct measurement technique referred to above. Both techniques benefit from using a full spectrum; i.e, by monitoring transmissivity over a wide range of wavelengths, and spectral recognition and quantification algorithms can also be used. However, while apparatus using these techniques can give accurate results, it is likely to be expensive, primarily because of the cost of suitable optical detectors.
As with the second technique described above, the present invention exploits the effect that glucose and other analytes have on the water vibration and combination overtone lines in predominantly aqueous solutions such as blood. At certain predeterminable wavelengths, the optical characteristics of such a solution exhibit readily quantifiable changes from which can be derived an indication of the concentration of the analyte in the solution. For example, when glucose is added to water, the vibration overtone/combination features of the water are reduced in magnitude in the absorption spectrum. This is because the glucose molecules replace some of the water; i.e. the relative molecule occupied by the water is reduced. There are also other changes to the shape of the water overtones due to the ice-like structure of water molecules around the solute. The net result of these effects is that at least two specific wavelengths, there is a substantial variation in the transmissivity of the solution relative to a reference level at which for another identifiable wavelength the transmissivity is unaltered.
According to the invention, a device for the in vivo measurement of the concentration of an analyte in an aqueous solution comprises a transmitter for illuminating a body part with light at a plurality of predetermined wavelengths; a detector for receiving light from such body part and generating input signals representative of the intensity of received light at each of the predetermined wavelengths; and a computer coupled to the detector for generating an output signal representative of the analyte concentration in the body part by analysis of the input signals received from the detector.
The detector in preferred devices of the invention is adapted to generate input signals representative of the intensity of light received at three discrete wavelengths. A suitable formula for calculating the output signal (So) from light received at three discrete wavelengths is as follows:       S    o    =            log      ⁢                        I          B                          I          A                      -                  I        C                    I        A            
where IA is representative of the intensity of received light a reference wavelength A, upon which the analyte has little effect;
IB is representative of the intensity of received light as a second wavelength B at which the presence of the analyte has the effect of increasing the transmissivity of the solution; and
IC is representative of the intensity of received light at a third wavelength C upon which the presence of the analyte has the effect of reducing the transmissivity of the solution,
and wherein C greater than B greater than A.
For glucose in water or blood, wavelength A is typically 810 nm; wavelength B is 970 nm; and wavelength C is 1053 nm. A particular advantage of wavelengths in this range is that relatively inexpensive detectors such as silicon diodes, can be used.
In the above description of the technique of the invention, reference has been made primarily to the transmissivity of the aqueous solution. Indeed, the operation of a device embodying the invention can best be understood by reference to direct transmission, and measurements can be made of sugar concentrations in blood for example, by monitoring the transmissivity of light through a body part such as a finger or an ear lobe. However, the technique is equally applicable when diffused light reflected from a part of the body is monitored rather than light which has been transmitted through a body part. In this respect it should be recognised that a diffuse reflectance spectrum from a scatterer such as body tissue is a quasi-absorption spectrum because of the multiplicity of the scattering.
Devices embodying the invention can use polychromatic (white) light as the source of illumination with appropriate filters disposed in front of the detectors for each selected wavelength. This is a very simple arrangement, but could be prone to errors in condition of high background light and is likely to suffer from a poor signal/noise ratio. A more preferred arrangement uses tuned laser diodes or light emitting diodes with appropriate filtering as respective light sources. The advantage is that the transmitted or reflected light can be detected using a single photodiode. Established analytical techniques can be used to derive a concentration signal using the formula set out above. Whatever the nature of the light source or sources used, we have found that stable output light intensity is important. Preferably the light intensity should be stabilized to one part in 10,000. Stabilization can be carried out over time periods of thirty minutes. Alternatively, means may be provided for monitoring the light output intensity and for effecting correction as required.
Devices embodying the invention can take a number of forms. xe2x80x9cTransmissionxe2x80x9d devices can comprise a light clamping mechanism for fitting over an ear lobe or finger for example, and where applied to a body part with significant bone content, provision may be made for squeezing the body part to project a fleshy section into the path of the transmitted light. Another such device takes the form of an enclosure fitted with transmission and detection apertures, into which a respective body part is inserted. In all these cases, effective optical contact between a respective body part and the transmitter and detector respectively can be enhanced by the provision of an index matching fluid between them, which has the effect of minimising the influence of extraneous light, and collimating light within the optical circuit.
Devices embodying the invention and using the diffuse reflectance variation can be of relatively more simple construction in that the point from which light is transmitted to the body part and the point at which reflected light is received can be located adjacent one another on the same instrument, typically in the same plane. Smaller amounts of impedance matching fluid can be required, and these variations of the device have the added advantage of being suitable for application to many parts of the body with relatively little concern for the presence of bone. They can also be used inside the mouth, where the exposed tissue is particularly well suited for measurement of blood characteristics. Further, reflectance devices may be adapted to include a pressure monitor for gauging the compliance of the skin being contacted. This itself is an indication of the nature of the tissue under examination and the quantity of blood flowing therein. Of course, the greater the concentration of blood in the relevant tissue section, the more accurate can be the analysis of analyte concentrations in the blood.
Devices embodying the invention can be constructed for personal use by individuals needing to regularly monitor their blood sugar levels, such as diabetes sufferers. Discrete devices for hand use can be provided but in some variants, the device can be attached or worn at substantially all times to enable the user to continuously monitor the relevant concentrations. For example, the device could be strapped to the body in the same manner as is a wrist watch. A device may also be equipped with an alarm which activates in response to dangerous changes in a sugar level, and a monitoring device with this feature will be of particular value for use with a sleeping subject.